Current research shows involvement of mitochondria in variety of pathological situations. In several instances of acute cell death to cardiac myocytes, neurons, hepatocytes and other cell types caused by hypoxia/ischemia and the toxicity of oxidant chemicals, excitotoxins, alcohol, doxirubicin, hydrophobic bile acids and Reye-related drugs, opening of high conductance permeability transition pores in the mitochondrial inner membrane leads to mitochondrial depolarization, release of ions, uncoupling of oxidative phosphorylation, permeation of solutes and, ultimately, cell killing. Onset of this mitochondrial permeability transition also activates the machinery for apoptosis. Release of cytochrome c after onset of the mitochondrial permeability transition activates proteases and endonucleases of the apoptotic program. The anti-apoptotic proto-oncogene, Bcl-2, encodes a protein that localizes to mitochondria and prevents onset of the mitochondrial permeability transition. Inherited and acquired defects of the mitochondrial genome are linked to impaired mitochondrial energy production, increased mitochondrial oxygen free radical generation and cell death in aging, neurodegenerative diseases and maternally inherited mitochondrial disorders. These examples illustrate how mitochondrial dysfunction underlies a wide spectrum of disease. Understanding of the basic mechanisms underlying mitochondrial dysfunction can lead to a better understanding of pathophysiologic processes and new strategies for prevention and treatment. The purpose of this conference is to bring together leading researchers studying mitochondrial dysfunction in many different disease settings to share ideas and recent research findings. The conference organizers are Dr. John J. Lemasters of the University of North Carolina and Dr. Anna-Liisa Nieminen of Case Western Reserve University. The proposed conference will be held January 15-20, 2000 in Santa Fe, New Mexico.